Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;41(4):400-408.
doi: 10.1002/pd.5796. Epub 2020 Nov 4.

A novel method for noninvasive diagnosis of monogenic diseases from circulating fetal cells

Liang Chang  1   2   3   4 , Xiaohui Zhu  1   3 , Rong Li  1   2   3   4 , Han Wu  5 , Weijian Chen  5 , Jiucheng Chen  5 , Hu Liu  5 , Shunjie Li  5 , Ping Liu  1   2   3   4
Affiliations

A novel method for noninvasive diagnosis of monogenic diseases from circulating fetal cells

Liang Chang et al. Prenat Diagn. 2021 Mar.

Abstract

Objective: To establish a method for noninvasive fetal cell isolation from maternal blood and prenatal testing of monogenic diseases by a combination of direct sequencing and targeted NGS-based SNP haplotyping from single fetal cells.

Method: Peripheral blood of pregnant women in two families (congenital deafness and ichthyosis) was collected. After density-based separation and immunostaining with multiple biomarkers, candidate fetal cells were identified by high-throughput imagine analysis and picked up by automation. Individual fetal cells were subjected to STR-genotyping to identify their origin. Pathogenic mutations were identified by direct Sanger sequencing, and a combination of targeted NGS and SNP haplotyping using a custom panel. All the results were compared with amniotic fluid DNA.

Results: Fetal trophoblasts were successfully harvested from maternal blood. STR-genotyping confirmed the fetal origin. Direct sequencing of pathogenic genetic mutations in fetal cells showed consistent results with amniotic fluid samples. For congenital deafness family, NGS-based SNP haplotyping also correctly identified the fetal haplotype. This single cell haplotyping method can be used to diagnose various genetic diseases.

Conclusion: We have established a method for noninvasive prenatal testing of monogenic diseases from circulating trophoblast cells. This cell-based NIPT can be further applied to the prenatal diagnosis of various monogenic diseases.

PubMed Disclaimer

References

REFERENCES

    1. Lo YM , Corbetta N , Chamberlain PF , et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485-487.
    1. Zhang J , Li J , Saucier JB , et al. Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA. Nat Med. 2019;25(3):439-447.
    1. Liang D , Cram DS , Tan H , et al. Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes. Genet Med: Off J Am Coll Med Genet. 2019;21(9):1998-2006.
    1. Taglauer ES , Wilkins-Haug L , Bianchi DW . Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta. 2014;35:S64-S68.
    1. WHO. Human Genomics in Global Health. https://www.who.int/genomics/public/geneticdiseases/en/. Accessed December 23, 2019.

LinkOut - more resources